The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.     

Treatment of chronic cardiac insufficiency with coenzyme Q10, results of meta-analysis in controlled clinical trials

Meta-analysis applied to eight controlled clinical trials of coenzyme Q10 (CoQ10)-treatment of congestive heart failure revealed a significant improvement a several important cardiac parameters such as ejection fraction (EF), stroke volume (SV), cardiac output (CO), cardiac index (CI) and end diastolic volume index (EDVI). Concerning the improvement in SV and CO the average patient in the CoQ10 group had a higher score than respectively 76% and 73% of the patients in the placebo group. The improvement in CO and SV was also significant when considering of homogeneity. Additional controlled clinical trials seem justified which may strengthen the power of the meta-analyses. However, based on available results, it can not be excluded that CoQ10 may have a future role a adjunctive therapy in a dosage of 100-200 mg/day in the treatment of chronic congestive heart failure.     

Autosensitized Photooxidation of the Rose Hip (Wild Rose) Oil - Mechanism and Quantum Yield for Singlet Molecular Oxygen O2 (1 Δg) Generation

The autosensitized photooxidation of the fatty acid components of rose hip (Wild Rose) oil was studied. Two important facts arise from the present investigation: a) Fatty acids of rose hip oil decompose upon visible light irradiation in the absence of external sensitizers by a mechanism that involves O₂(¹Δ_g). The pigments present in rose hip oil themselves efficiently sensitize the generation of O₂(¹Δ_g) with a quantum yield of 0.038 (upper limit). b) Visible irradiation also produces the degradation of the anthocyanines, native pigments which could behave as O₂(¹Δ_g) sensitizers in the oil. In this case a mechanism involving the production of superoxide ions by the pigment and further attack of the radicals on the phenol groups of the anthocyanine could account for the observed experimental evidences. These results should be carefully considered in a practical sense when rose hip oil is stored or employed under daylight conditions. Exposure to visible radiation may cause irreversible transformations in rose hip oil.     

Clinical pharmacology and malaria

The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs.     

The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation

cABL is a protooncogene, activated in a subset of human leukemias, whose protein product is a nonreceptor tyrosine kinase of unknown function. cABL has a complex structure that includes several domains and motifs found in proteins implicated in signal transduction pathways. An approach to elucidate cABL function is to identify proteins that interact directly with cABL and that may serve as regulators or effectors of its activity. To this end, a protein-interaction screen of a phage expression library was undertaken to identify proteins that interact with specific domains of cABL. An SH3-domain-containing protein has been identified that interacts with sequences in the cABL carboxyl terminus. The cDNA encoding ALP1 (amphiphysin-like protein 1) was isolated from a 16-day mouse embryo. ALP1 has high homology to BIN1, a recently cloned myc-interacting protein, and also shows significant homology to amphiphysin, a neuronal protein cloned from human and chicken. The amino terminus has homology to two yeast proteins, Rvs167 and Rvs161, which are involved in cell entry into stationary phase and cytoskeletal organization. ALP1 binds cABL in vitro and in vivo. Expression of ALP1 results in morphological transformation of NIH 3T3 fibroblasts in a cABL-dependent manner. The properties of ALP1 suggest that it may be involved in possible cytoskeletal functions of the cABL kinase. Additionally, these results provide further evidence for the importance of the cABL carboxyl terminus and its binding proteins in the regulation of cABL function.     

Metabolic impact of adenovirus-mediated overexpression of the glucose-6-phosphatase catalytic subunit in hepatocytes

Glucose-6-phosphatase (G6Pase) catalyzes the hydrolysis of glucose 6-phosphate (Glu-6-P) to free glucose and, as the last step in gluconeogenesis and glycogenolysis in liver, is thought to play an important role in glucose homeostasis. G6Pase activity appears to be conferred by a set of proteins localized to the endoplasmic reticulum, including a glucose-6-phosphate translocase, a G6Pase phosphohydrolase or catalytic subunit, and glucose and inorganic phosphate transporters in the endoplasmic reticulum membrane. In the current study, we used a recombinant adenovirus containing the cDNA encoding the G6Pase catalytic subunit (AdCMV-G6Pase) to evaluate the metabolic impact of overexpression of the enzyme in primary hepatocytes. We found that AdCMV-G6Pase-treated liver cells contain significantly less glycogen and Glu-6-P, but unchanged UDP-glucose levels, relative to control cells. Further, the glycogen synthase activity state was closely correlated with Glu-6-P levels over a wide range of glucose concentrations in both G6Pase-overexpressing and control cells. The reduction in glycogen synthesis in AdCMV-G6Pase-treated hepatocytes is therefore not a function of decreased substrate availability but rather occurs because of the regulatory effects of Glu-6-P on glycogen synthase activity. We also found that AdCMV-G6Pase-treated-cells had significantly lower rates of lactate production and [3-3H]glucose usage, coupled with enhanced rates of gluconeogenesis and Glu-6-P hydrolysis. We conclude that overexpression of the G6Pase catalytic subunit alone is sufficient to activate flux through the G6Pase system in liver cells. Further, hepatocytes treated with AdCMV-G6Pase exhibit a metabolic profile resembling that of liver cells from patients or animals with non-insulin-dependent diabetes mellitus, suggesting that dysregulation of the catalytic subunit of G6Pase could contribute to the etiology of the disease.